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Home Heart Transplantation Antibody treatment before surgery may prevent heart transplant rejection

Antibody treatment before surgery may prevent heart transplant rejection

by Science Blog
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In mice, an approach that blocks inflammation extends organ survival from about a week to more than two months

A new study by scientists at Cincinnati Children's Hospital shows there may be a way to further protect transplanted hearts from rejection by preparing the donor organ and recipient with anti-inflammatory antibody treatment before surgery. Suggests.

The survey results are Published online in PNASfocuses on blocking the innate immune response that normally occurs in response to microbial infection. The same reaction has been shown to cause dangerous inflammation in transplanted hearts.

In a new study in mice, transplanted hearts worked longer when recipients also received a new antibody treatment. The first of a complex series of steps is now underway to determine whether a similar approach can be safely implemented for human heart transplants.

“The anti-rejection therapies currently in use are broad-spectrum immunosuppressants that make patients more susceptible to infections. By using specific antibodies, they simply block the inflammation that leads to rejection, and the anti-bacterial immune system We believe that it can be left as is,” says the corresponding author. Chandrashekar Pathare, DVM, Ph.D.Director of the Division of Immunobiology at Cincinnati Children's Hospital.

Makes memory T cells slightly easier to forget

The research team, which includes lead author Irene Saha, Ph.D., a researcher at the Passare Institute, and several colleagues at Cincinnati Children's Hospital, investigated how dendritic cells in donor organs trigger an inflammatory response in the recipient's body. focused.

Specifically, the research team found that recipient memory CD4 T cells activate donor dendritic cells through signals conveyed by the proteins CD40L and TNFα. Blocking this signaling pathway using gene editing techniques resulted in reduced inflammation and increased survival of transplanted hearts.

In this study, untreated mice rejected the donated hearts within a week. However, the mice gene-edited to lack the CD40L and TNFα receptors maintained strong heart function until the experiment ended on day 66.

“We’ve been working on this for almost 10 years,” Passare said. “The main reason we elucidated this pathway was to focus on understanding how recipient memory T cells with potential reactivity to donor-specific antigens induce innate inflammation. The rest of the field focuses on other concepts such as ischemia-reperfusion injury, ligands from dead cells, and innate immune receptors, all of which actually cause transplant rejection. It seems not.”

Dr. Passare continued: “The key to preventing organ rejection is to deprive the recipient's memory T cells of their ability to initiate inflammation when they recognize donor antigens in dendritic cells. T cell memory is essential to fight infection. However, innate inflammation caused by memory T cells is detrimental to the survival of transplanted organs.

next step

The co-authors believe that the process they used to protect the heart from rejection could be applied to other forms of organ transplants.

However, gene editing performed in mice is not considered safe for humans. So the research team is now evaluating other ways to interfere with the inflammatory response.

“Using blocking antibodies against CD40 could be a good approach. Another option is to create biologics or compounds that specifically target the human TNF receptor superfamily,” says Passare. he says. “I think this is a very interesting area for future drug development.”

About research

Cincinnati Children's co-authors include Dr. Amanpreet Singh Chawla, a former postdoctoral fellow in Pathare's lab. Dr. Ana Paula Oliveira, Postdoctoral Fellow at the Hagan Institute. Eileen Elfers, BS, research assistant in the Katz lab. Kathryn Wallick, BS, MSTP student in the Passare lab. Dr. Hannah Mavers, former graduate student at the Passare Institute; Dr. Thomas Hagan, Division of Infectious Diseases. Dr. Jonathan Katz, Department of Immunobiology;

Funding sources for this study included grants from the National Institutes of Health (R01 AI123176, R01 AI155426, and U54 DK126108). This research was also supported by the Cincinnati Children's Hospital Veterinary Services Facility, Research Flow Cytometry Core, and Bioinformatics Collaborative Services Core.

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Welcome to Daily Transplant News, your trusted source for the latest updates, stories, and information on transplantation and organ donations. We are passionate about sharing the inspiring journeys, groundbreaking research, and invaluable resources surrounding the world of transplantation.

About Us

Welcome to Daily Transplant News, your trusted source for the latest updates, stories, and information on transplantation and organ donations. We are passionate about sharing the inspiring journeys, groundbreaking research, and invaluable resources surrounding the world of transplantation.

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